Process for the production of guanidine and derivatives thereof



United States Patent Ofiice 2,884,437 Patented Apr. 28, 1959 2,884,437 PROCESS FOR THE PRODUCTION OF GUANIDINE AND DERIVATIVES THEREOF Elwyn Roberts, London, England, assignor to the Minister of Supply, in His Majestys Government of the United Kingdom of Great Britain and Northern Ireland, London, England No Drawing. Application September 4, 1951 Serial No. 245,081

9 Claims. (Cl. 260-459) The present invention relates generally to a method for producing guanidine and derivatives thereof, and is related to my copending application for substituted guanidines Serial Number 245,080, filed September 4, 1951, now abandoned, which is a continuation in part hereof.

Guanidine and many of its derivatives have become of considerable interest in the art of military explosives. For example, nitroguanidine is itself a high explosive, and when suitably mixed with a nitrocellulose carrier it serves as an excellent projectile propellant. As a high explosive, nitroguanidine is characterized by a flashless explosion of obvious strategic advantage in military use, and as a propellant it is found to reduce gun barrel corrosion by a substantial amount from that obtained with other common propellant explosives. These characteristics therefore make nitroguanidine a highly desirable explosive from the military standpoint, While other derivatives of guanidine impart similar attributes to conventional explosive compositions when mixed therewith.

Although a plurality of methods for the production of guanidine and its derivatives have been attempted and suggested in the prior art, no method has heretofore been found which enables the practical large scale production of guanidine and its derivatives. It is accordingly one object of the present invention to provide a commercially feasible, economical, and practical process for the production of gu'anidine and its derivatives, which lends itself to large scale production thereof.

Another object of the present invention is to provide a process for the production of guanidine and derivatives thereof from urea.

Another object of the present invention is to provide a process for the production of guanidine and such derivatives thereof as guanidinium salts, guanidinium alkyl sulfate, and nitrogu'anidine.

Other objects and advantages of the present invention will become apparent to those skilled in the art from a consideration of the following description of the process and variations therein embraced by the present invention.

According to the present invention there is provided a process for the production of guanidine and derivatives thereof which includes the steps of interacting urea and dialkyl sulfate to form an alkyl isourea alkyl hydrogen sulfate, and aminating this reaction product with ammonia to form gu'anidinium alkyl sulfate, as may be represented by the following equations wherein R is used to denote 15H: l fiz Such dialkyl sulfates as dimethyl-, diethyl-, di-n-propyland di-n-butyl sulfate have been found to be advantageous etherifying agents. When using these several etherifying agents in a one to one molar ratio with urea, it has been found that the conversions of urea to guanidinium alkyl sulfate are ca. 65, 73, 72 and 73%, respectively. The use of diethyl sulfate is, however, preferred because of its nontoxic nature and availability. It has been further found that the etherification or alkylation using a dialkyl sulfate proceeds best in the absence of any diluent or alkali; indeed if water or alkali be employed no alkylation takes place, which is contrary to the usual experience of alkylation using this kind of reagent.

The production of alkyl isourea allyl hydrogen sulfate is advantageously carried out by gradually adding urea to heated anhydrous alkyl sulfate in substantially equimolar proportions under conditions of vigorous agitation. The reaction mixture is maintained at a temperature of between and 130 C., external cooling being necessary after the reaction is initiated owing to the slight exo thermic character thereof. Completion of the reaction is effected by maintaining the above temperature range for a further period, the time necessary being a function of temperature. The lower the reaction temperature the more prolonged the period. For example, about one hour heating period is required at C., a 30 minute period at C., and a 15-20 minute period at C. Best results are obtained, however, by employing a temperature of 100 to 110 C.

Amination of the alkyl isourea alkyl hydrogen sulfate is effected by treating the mixture resulting from the above reaction with ammonia at a temperature not exceeding 65 C. and preferably of about 60 C. The ammonia may be employed in any desired form, for example as an aqueous or alcoholic solution, but it is preferred to employ the gas, passing it into the alkylated reaction product at such a rate that it is completely absorbed and until amination is complete. Since the gaseous amination is exothermic, it is carried out with cooling to maintain the desired reaction temperature. When using diethyl sulfate as the etherifying agent for example, amination is usually complete after passing ammonia for 'a further period of one hour at 60 C. following the conclusion of the exothermic stage of the reaction. The concentration of ammonia in the system when amination is complete is ca. 2.6%. Finally, the reaction mixture is freed from the alcohol by-product of amination and excess ammonia by distillation, leaving a residue comprising primarily guanidinium alkyl sulfate.

If an aqueous ammoniacal solution is employed, the alkylated reaction product is advantageously treated with an excess of ammonia, preferably up to 20% excess, and heated to 60 C. for a period of about three hours. Guanidinium alkyl sulfate is obtained by evaporating the solution under vacuum to dryness.

The isolation of guanidine is effected according to the invention by dissolving the residue of guanidinium alkyl sulfate in anhydrous ethyl alcohol and treating the alcoholic solution with an alkali such as a solution of an alkali alcoholate. The resultant alkali alkyl sulfate precipitates and can be separated by filtration, leaving a solution of guanidine in alcohol. The alcoholic solution can be distilled in vacuo to yield a residue of guanidine containing but slight impurity. The loss of guanidine by this treatment is almost negligible. This reaction may be represented by the following equation, using potassium ethylate as representative of the alkali alcoholates in general, and wherein R denotes an alkyl radical:

The isolation of various guanidine salts is effected according to the invention by neutralization of the alcoholic solution of guanidine with the appropriate acid, followed by crystallization. When neutralization is effected, forexample, with nitric acid, the corresponding salt, guanidinium nitrate, is formed and can be isolated almost quantitatively by the usual procedure of fractional crystallization, as represented by the following equation:

Nitroguanidine may be produced using guanidine prepared as disclosed above, but it is advantageously produced by a simple modification which does not involve isolating the guanidine itself. I have found that guanidine alkyl sulfate may be treated directly with a nitrating mixture and nitroguanidine thereby obtained in good yield, as indicated by the following equation wherein R denotes an alkyl radical:

GENO;

fractionation CNH2 -H2SO ROH HNO: [I r C-NHNOr E20 H280 (H2804) l The conversion of guanidinium ethyl sulfate to guanidinium hydrogen sulfate and alcohol by acid hydrolysis is rapid and quantitative, and removal of alcohol and water may be conveniently effected owing to the considerable stability of guanidine solution in concentrated sulphuric acid at elevated temperature. This latter process, although longer than the former process for producing nitroguanidine, has the advantage thereover of enabling recovery as alcohol of both alkyl radicals from the dialkyl sulfate employed, which can then be recycled if necessary, and the further advantage that after the hydrolysis step the sulfate radical of the dialkyl sulfate is present in the form of sulfuric acid and is advantageously employed at the nitration stage.

The present invention is further illustrated by the following specific examples:

Example I Dimethyl sulfate, 126 parts by weight, is heated to 100 C., and urea, 60 parts by weight, is added thereto with efficient stirring within a period of about 15 minutes, keeping the temperature constant by slight cooling as the reaction between the two ingredients, once started, be comes exothermic. After addition of the urea, the reaction mixture is held at 110 C. for 5 minutes and then cooled to 80 C. Water, 100 parts by weight, is added fairly rapidly to the well stirred reaction mixture when the temperature drops appreciably. The diluted reaction mixture is then cooled to ordinary room temperature.

The aqueous reaction solution contains 48.5 parts by weight of O-methyl isourea, as the salt of methyl hydrogen sulfate, corresponding to a yield of 66% of theory based on urea; the solution also is acidic, the acidity corresponding to 25-26 parts by weight of methyl hydrogen sulfate. The aqueous reaction mixture is next neutralized with concentrated (0.880) ammonia using methyl red indicator, and to the neutral solution is added 50 parts by volume of concentrated (0.880) ammonia, approximately 20% excess ammonia on the methyl isourea content. The resultant mixture is then heated to 60 C. and held at this temperature for three hours, then cooled to room temperature. After this treatment, the aqueous solution contains 37.7 parts by weight of guanidine as the salt of methyl hydrogen sulfate, corresponding to a yield of about 64% of theory based on urea. The aqueous solution containing guanidinium methyl sulfate is evaporated to dryness in vacuo (bath temperature 60l00 C., pressure 20-30 mm. of mercury). The residue, 173 parts by weight, which is molten at C., is a waxy solid at room temperature and consists of fairly pure guanidinium methyl sulfate.

.Example II Free guanidine may be obtained from the guanidinium methyl sulfate residue obtained as in Example I as follows:

The guanidinium methyl sulfate residue is dissolved in 1000 parts by volume of ethyl alcohol (grade I) by warming, and the alcoholic solution then cooled to ordinary room temperature. With stirring and cooling to lO-20 C., 470 parts by volume of a solution containing 11.34 parts potassium hydroxide in 100 parts by volume of ethyl alcohol (grade I) is added to the alcoholic guanidinium solution. Potassium methyl hydrogen sulfate, 139 parts by weight, is precipitated by this treatment, separated by filtration, and washed with cold alcohol until free from occluded guanidine. The alcoholic filtrate contains 35.9 parts by weight of guanidine, corresponding to a yield of about 61% of theory based on urea. The alcoholic solution of guanidine can, if desired, be evaporated in vacuo to small bulk, or even until all alcohol is expelled, with no loss of yield of guanidine.

Example III with alcohol, the weight ratio of solid to mother liquor being about 1:1. The yield of solid guanidine nitrate is 5354% based on urea. A further quantity of guanidine nitrate can be recovered by fractional crystallization from the mother liquor.

Example IV To prepare nitroguanidine, guanidinium methyl sulfate is prepared as set forth in Example I, the product being a waxy solid consisting predominantly of the guanidinium methyl sulfate. 10 parts by Weight of this solid are slowly added to a nitrating mixture of 20 parts of 99% sulphuric acid and 3 parts by weight of 99% nitric acid at 10-15" C. with stirring. The time of addition is about 5 minutes. The reaction mixture is warmed to 40 C. and held at this temperature for 30 minutes. It is then cooled to 20 C. and poured on to parts of a mixture of ice and water. A precipitate is thrown down which is collected, washed with water, and then transferred to a vessel and again treated with 30 parts of water, insuring that any nitrog uanidine sulfate present is converted to nitroguanidine. The solid is again collected, washed Well with water, and dried. The weight of the solid product is 1.82 parts, corresponding to a yield of 31.2% of nitroguanidine based on urea. The melting point of the resulting nitrogames-"1 5 guanidine when recrystallized from water is 225' C. (uncorrected) Example V As an alternative process of producing nitrognanidine, urea, 240 parts by weight, is added to diethyl sulfate, 616 parts by weight, at ordinary room temperature and the suspension heated with efficient stirring to a temperature of 100 C. to produce O-ethyl isourea. The mixture becomes clear after about 9 minutes. Reaction at this state is somewhat exothermic but the temperature is readily controlled. All evolution of heat ceases after about 16 minutes, but the reaction mixture is maintained at 100 C. for a total period of 60 minutes, after which it is cooled to 60 C. The conversion of urea to O-ethyl isourea is 73%. Dry ammonia gas is then passed fairly rapidly into the well stirred slightly super cooled reaction mixture (F.P. 64 C.) at 60 C., efficient cooling being necessary to maintain this temperature, to produce guanidinium ethyl sulfate. Ammonia gas is passed for a total period preferably of two and one half hours, during which time 86.4 parts by weight should be absorbed. The mixture is then allowed to stand at 60 C. for a period of one hour. On cooling crystallization commences at 47 C. The reaction mixture is finally heated to 100 C. under a pressure of 1 cm. of mercury, whereby all the alcohol, 149.9 parts by weight, and excess ammonia, 15.0 parts by weight, contained in the reaction mixture are distilled, and may be collected in cold trap if desired. The conversion of O-ethyl isourea to guanidinium ethyl sulfate is quantitative. The residue (F.P. 94 C.), 772.5 parts by weight, consisting primarily of guanidinium ethyl sulfate, may be converted into guanidine as in Example II, or if a guanidine derivative such as nitroguanidine is desired, hydrolysis of the guanidinium ethyl sulfate may be performed as follows. Sulphuric acid, 76.7 parts by weight, and water, 155.4 parts by weight, are added to the guanidine ethyl sulfate, and-the mixture is boiled with refluxing for about 30 minutes. The boiling point of the liquid falls from about 118 to 104 C., and the hydrolysis is judged to be complete when a steady minimum for the boiling point of the liquid is attained. The liquid is then carefully fractionated at normal atmospheric pressure until the boiling point reaches 120-125 C., indicating that a large proportion of alcohol liberated during hydrolysis is recovered. All remaining alcohol and water is then distilled under diminished pressure down to 20-30 mm. of mercury at a bath temperature of 100 C. This hydrolysis of guanidinium ethyl sulfate to guanidinium hydrogen sulfate is quantitative. The resulting residue (F.P. 64 C.), 757.7 parts by weight, and consisting primarily of guanidinium hydrogen sulfate is then converted to nitroguanidine by adding thereto concentrated (98%) sulphuric acid, 844.3 parts by weight, with stirring, cooling to C., and then adding 98.5% nitric acid, 258.6 parts by weight, slowly with efficient stirring, the temperature being maintained below 25 C. by external cooling. Best results are obtained by nitrating at 10 C. for 30 minutes. The resultant nitroguanidine is isolated from the nitration mixture by adding it slowly to a mixture of ice and water, 5093 parts by weight, whereby the crude nitroguanidine, 273.8 parts by weight, is precipitated. The solid product is recovered by filtration and freed from acid mother liquor (ca. H 80 concentration) by washing preferably with a saturated aqueous solution of nitroguanidine at normal room temperature. This crude nitroguanidine is purified by recrystallization from water saturated at normal room temperature with nitroguanidine, yielding 262.6 parts by weight of pure nitroguanidine. The conversion of guanidinium hydrogen sulfate to elude nitroguanidine on nitration is 90-91%; and the yield of purified nitroguanidine based on urea is ca. 63%.

Having thus disclosed generally a process for producing guanidine and the nature of variations in that process which may be employed for producing derivatives of guanidine, together with specific examples thereof, it is not intended to limit the scope of the present invention to the details of the specific embodiments described, as modifications thereof within the spirit and scope of the appended claims will be apparent to those skilled in the art.

What is claimed is:

1. The process for the production of guanidinium alkyl sulfates comprising the steps of reacting urea with a dialkyl sulfate chosen from the group consisting of dimethyl-, diethyl-, di-n-propyl-, and di-n-butylsulfate to produce an alkyl isourea alkyl hydrogen sulfate, and reacting the said alkyl isourea alkyl hydrogen sulfate with ammonia for 1-3 hours at about 60 C. to produce the corresponding guanidinium alkyl sulfate thus obtained to produce guanidinium alkyl sulfate.

2. The process for the production of nitroguanidine comprising the steps recited in claim 1 and in addition the step of reacting the said guanidinium alkyl sulfate with a nitrating mixture comprising nitric and sulphuric acids to produce nitroguanidine.

3. In a process for producing nitroguanidine the steps described in claim 1 and in addition reacting the said guanidinium alkyl sulfate with a nitrating mixture to produce nitroguanidine.

4. In a process for producing nitroguanidine the steps described in claim 1 and in addition the steps of hydrolyzing the said guanidinium alkyl sulfate to produce guanidinium hydrogen sulfate, and nitrating the said guanidinium hydrogen sulfate with a mixture comprising nitric and sulphuric acids to produce nitroguanidine.

5. In a process for producing nitroguanidine the steps described in claim 1 and in addition the steps of hydrolyzing the said guanidinium alkyl sulfate to produce guanidinium hydrogen sulfate, and nitrating the said guanidinium hydrogen sulfate to produce nitroguanidine.

6. In a process for producing guanidine the steps described in claim 1 and in addition reacting the said guanidinium alkyl sulfate with an alkali alcoholate to produce guanidine.

7. In a process for producing guanidine the steps described in claim 1 and in addition reacting the said guanidinium alkyl sulfate with an alkali to produce guanidine.

8. In a process for producing guanidine salt the steps described in claim 1 and in addition reacting the said guanidinium alkyl sulfate with an alkali alcoholate to produce an alcoholic solution of guanidine, and neutralizing the said solution with an acid to produce the corresponding guanidine salt.

9. The process for the production of guanidinium alkyl sulfates comprising the steps of reacting urea with an anhydrous dialkyl sulfate selected from the group consisting of dimethyl-, diethyl-, di-n-propyl-, and di-n-butylsulfate to produce an alkyl isourea alkyl hydrogen sulfate, passing ammonia gas through the said alkyl isourea alkyl hydrogen sulfate for about one hour at about 60 C. to produce the corresponding guanidinium alkyl sulfate.

References Cited in the file of this patent UNITED STATES PATENTS 1,672,029 Heyn June 5, 1928 2,286,364 Jayne June 16, 1942 2,567,676 Marsh Sept. 11, 1951 FOREIGN PATENTS 448,796 Great Britain June 15, 1936 117,054 Australia June 17, 1943 OTHER REFERENCES Werner: J our. Chem. Soc.," London, vol. (1914), pp. 923-932.

Davis et al.: Jour. Amer. Chem. Society, vol. 55 (1933), pp. 731-740.

Stettbacher: Nitrocellulose, vol. 7 (1936), pp. 141- 145.

Barker: Jour. Chem. Soc." (1943), pages 101-104. 

1. THE PROCESS FOR THE PRODUCTION OF GUANIDINIUM ALKYL SULFATES COMPRISING THE STEPS OF REACTING UREA WITH A DIALKYL SULFATE CHOSEN FROM THE GROUP CONSISTING OF DIMETHYL-, DIETHYL-, DI-N-PROPYL-, AND DI-N-BUTYLSULFATE TO PRODUCE AN ALKYL ISOUREA ALKYL HYDROGEN SULFATE, AND REACTING THE SAID ALKYL ISOUREA ALKYL HYDROGEN SULFATE WITH AMMONIA FOR 1-3 HOURS AT ABOUT 60*C. TO PRODUCE THE CORRESPONDING GUANIDINIUM ALKYL SULFATE THUS OBTAINED TO PRODUCE GUANIDINIUM ALKYL SULFATE.
 3. IN A PROCESS FOR PRODUCING NITROGUANIDINE THE STEPS DESCRIBED IN CLAIM 1 AND IN ADDITION REACTING THE SAID GUANIDINIUM ALKYL SULFATE WITH A NITRATING MIXTURE TO PRODUCE NITROGUANIDINE.
 7. IN A PROCESS FOR PRODUCING GUANIDINE THE STEPS DESCRIBED IN CLAIM 1 AND IN ADDITION REACTING THE SAID GUANIDINIUM ALKYL SULFATE WITH AN ALKALI TO PRODUCE GUANIDINE. 